Center for Experimental Medical Research, the Third Xiangya Hospital of Central South University, Changsha, China.
Department of Cardiology, the Third Xiangya Hospital of Central South University, Changsha, China.
J Cell Mol Med. 2020 Sep;24(18):10290-10301. doi: 10.1111/jcmm.15744. Epub 2020 Aug 17.
There are many different types of cardiovascular diseases, which impose a huge economic burden due to their extremely high mortality rates, so it is necessary to explore the underlying mechanisms to achieve better supportive and curative care outcomes. Sphingosine 1-phosphate (S1P) is a bioactive lipid mediator with paracrine and autocrine activities that acts through its cell surface S1P receptors (S1PRs) and intracellular signals. In the circulatory system, S1P is indispensable for both normal and disease conditions; however, there are very different views on its diverse roles, and its specific relevance to cardiovascular pathogenesis remains elusive. Here, we review the synthesis, release and functions of S1P, specifically detail the roles of S1P and S1PRs in some common cardiovascular diseases, and then address several controversial points, finally, we focus on the development of S1P-based therapeutic approaches in cardiovascular diseases, such as the selective S1PR1 modulator amiselimod (MT-1303) and the non-selective S1PR1 and S1PR3 agonist fingolimod, which may provide valuable insights into potential therapeutic strategies for cardiovascular diseases.
有许多不同类型的心血管疾病，由于其极高的死亡率，给社会带来了巨大的经济负担，因此有必要探索潜在的发病机制，以实现更好的支持和治疗效果。鞘氨醇 1-磷酸（S1P）是一种具有旁分泌和自分泌活性的生物活性脂质介质，通过其细胞表面 S1P 受体（S1PRs）和细胞内信号发挥作用。在循环系统中，S1P 对正常和疾病状态都是必不可少的；然而，人们对其多种作用存在非常不同的看法，其与心血管发病机制的具体相关性仍不清楚。在这里，我们回顾了 S1P 的合成、释放和功能，特别详细介绍了 S1P 和 S1PRs 在一些常见心血管疾病中的作用，然后讨论了几个有争议的观点，最后，我们重点介绍了基于 S1P 的治疗方法在心血管疾病中的发展，如选择性 S1PR1 调节剂 amiselimod（MT-1303）和非选择性 S1PR1 和 S1PR3 激动剂 fingolimod，这可能为心血管疾病的潜在治疗策略提供有价值的见解。
